Beta‐amyloid protein (25–35) disrupts hippocampal network activity: Role of Fyn‐kinase

Early cognitive deficit characteristic of early Alzheimer's disease seems to be produced by the soluble forms of β‐amyloid protein. Such cognitive deficit correlates with neuronal network dysfunction that is reflected as alterations in the electroencephalogram of both Alzheimer patients and transgenic murine models of such disease. Correspondingly, recent studies have demonstrated that chronic exposure to βAP affects hippocampal oscillatory properties. However, it is still unclear if such neuronal network dysfunction results from a direct action of βAP on the hippocampal circuit or it is secondary to the chronic presence of the protein in the brain. Therefore, we aimed to explore the effect of acute exposure to βAP_25–35 on hippocampal network activity both in vitro and in vivo, as well as on intrinsic and synaptic properties of hippocampal neurons. We found that βAP_25–35, reversibly, affects spontaneous hippocampal population activity in vitro. Such effect is not produced by the inverse sequence βAP_35–25 and is reproduced by the full‐length peptide βAP_1–42. Correspondingly βAP_25–35, but not the inverse sequence βAP_35–25, reduces theta‐like activity recorded from the hippocampus in vivo. The βAP_25–35‐induced disruption in hippocampal network activity correlates with a reduction in spontaneous neuronal activity and synaptic transmission, as well as with an inhibition in the subthreshold oscillations produced by pyramidal neurons in vitro. Finally, we studied the involvement of Fyn‐kinase on the βAP_25–35‐induced disruption in hippocampal network activity in vitro. Interestingly, we found that such phenomenon is not observed in slices obtained from Fyn‐knockout mice. In conclusion, our data suggest that βAP acutely affects proper hippocampal function through a Fyn‐dependent mechanism. We propose that such alteration might be related to the cognitive impairment observed, at least, during the early phases of Alzheimer's disease. © 2009 Wiley‐Liss, Inc.     

基于三蝶烯架构的固有微孔聚酰亚胺网络的制备及其吸附特性

通过三氨基三蝶烯与3,4,9,10-苝四羧酸酐（PTCDA）、均苯四甲酸酐（PMDA）、3,3’,4,4’-联苯二酐（BPDA）以及螺环二酐（SBIDA）的缩聚反应分别合成了4种固有微孔聚酰亚胺材料(Trip-PIMs)。采用傅里叶红外光谱（FT-IR）、固体核磁碳谱（Solid-state 13C-NMR）、扫描电子显微镜（SEM）、热重分析(TG)和氮气吸附等测试手段表征了材料的微孔结构和物理化学性能,测试了材料对有机气体和液体的吸附性能。结果表明：三蝶烯结构的引入使材料获得了较高的比表面积,同时具有良好的溶胀特性;对比烷烃,该材料对胺类和苯类具有更高的吸附率;螺环结构的引入能进一步提高材料骨架的溶胀特性,从而提升材料的吸附能力。     

Modest antihypertensive effect of epanolol,a beta1-selective receptor blocker with beta1 agonist activity: An acute and long-term hemodynamic study at rest and during exercise and double crossover comparison with atenolol on ambulatory blood pressure

Summary Beta-blockers with less cardiodepressive effect than traditional nonselective beta₁₊₂-blocking agents could be useful in the treatment of hypertension, provided the reduction in blood pressure was satisfactory. Epanolol, a selective beta₁-receptor blocker with intrinsic sympathomimetic activity, induced a fall in intraarterial pressure of 8% at rest sitting and 11% during 100 W bicycle exercise after the first dose of 200 mg in 12 patients with essential hypertension. Heart rate, stroke index, and cardiac index initially fell by 14%, 11%, and 23%, respectively. The total peripheral resistance index increased by 21% after 2 hours, and then reverted towards the pretreatment level. After 10 months of epanolol treatment (mean 300 mg/day), the reduction in arterial pressure was 5% at rest and 10% during exercise. Cardiac index and heart rate were still reduced 14–21%, while total peripheral resistance was unchanged or slightly increased (2–10%). Twenty-four hour ambulatory blood pressure was higher on epanolol (300 mg/day) than on atenolol (150 mg/day) treatment (137/97 vs. 128/91 mmHg). Thus, the achieved blood pressure reduction induced by epanolol was moderate, while other characteristics of beta-receptor blockade, in particular, the reduction of heart rate and cardiac output, were maintained. This suggests that the compound may be useful for other cardioavascular disorders, e.g., angina pectoris in patients without hypertension or cardiac arrhythmia.     

Balloon-occluded retrograde transvenous obliteration improves liver function in patients with cirrhosis and portal hypertension

BACKGROUND AND AIM: Balloon-occluded retrograde transvenous obliteration (B-RTO) is a novel therapeutic method for the treatment of large gastric fundal varices with spontaneous splenorenal shunt (SRS). However, the effects of B-RTO on liver function remain unknown. METHODS: Fourteen patients with portal hypertension and gastric varices with SRS were studied, consisting of four patients with acute bleeding, five with high-risk varices, and five with refractory portosystemic encephalopathy. Hepatic venous catheterization was performed to evaluate hepatic blood flow and liver function using the continuous indocyanine green (ICG) infusion method. To assess the metabolic activity of the hepatocyte, the intrinsic clearance of ICG was calculated. In all patients, endoscopic study was performed before and 1 week and 1 month after the B-RTO, and followed every 6 months thereafter. After baseline measurements, B-RTO was performed. Four weeks after the B-RTO, the same catheter measurements were repeated. RESULTS: The B-RTO was successful in all patients. Contrast-enhanced computed tomography showed complete obliteration of the SRS prior to the follow-up measurements. Endoscopic eradication of the fundal varices was obtained 6 months after B-RTO in all patients and encephalopathy was improved within 1 week after B-RTO. Following the B-RTO, hepatic blood flow (441 +/- 214 vs 668 +/- 299 mL/min, P < 0.0001) and the intrinsic clearance of ICG (233 +/- 123 vs 285 +/- 148 mL/min, P < 0.05) were significantly increased. Furthermore, intrahepatic resistance decreased after the B-RTO (P < 0.005). CONCLUSION: From short-term assessment, B-RTO increases hepatic blood flow and improves the metabolic activity of the liver in patients with portal hypertension.     

基于局部场电位固有模态分量的响应调谐特性研究

局部场电位(LFP)反映了视觉刺激下大脑皮层局部区域神经元集群的响应.LFP响应特征的准确提取,对分析视觉信息的处理机制具有重要意义.本研究针对LFP的非平稳特性,采用具有自适应特征的希尔伯特黄变换,分解LFP固有模态分量,据此研究了大鼠Vl区对刺激光栅空间频率的响应调谐特性,并与多神经元锋电位(MUA)和小波分解提取的Gamma频带进行了对比.结果表明:LFP第二阶固有模态分量对刺激光栅空间频率的调谐特性最强,调谐指数的均值(0.795 1)高于MUA调谐指数(0.631 3)和小波分解调谐指数(0.6646),而且与MUA响应一致率达68.75％.所提出的方法在LFP响应频带特征提取上更有优势.     

The Self and Its Prolonged Intrinsic Neural Timescale in Schizophrenia

Schizophrenia (SCZ) can be characterized as a basic self-disorder that is featured by abnormal temporal integration on phenomenological (experience) and psychological (information processing) levels. Temporal integration on the neuronal level can be measured by the brain’s intrinsic neural timescale using the autocorrelation window (ACW) and power-law exponent (PLE). Our goal was to relate intrinsic neural timescales (ACW, PLE), as a proxy of temporal integration on the neuronal level, to temporal integration related to self-disorder on psychological (Enfacement illusion task in electroencephalography) and phenomenological (Examination of Anomalous Self-Experience [EASE]) levels. SCZ participants exhibited prolonged ACW and higher PLE during the self-referential task (Enfacement illusion), but not during the non-self-referential task (auditory oddball). The degree of ACW/PLE change during task relative to rest was significantly reduced in self-referential task in SCZ. A moderation model showed that low and high ACW/PLE exerted differential impact on the relationship of self-disorder (EASE) and negative symptoms (PANSS). In sum, we demonstrate abnormal prolongation in intrinsic neural timescale during self-reference in SCZ including its relation to basic self-disorder and negative symptoms. Our results point to abnormal relation of self and temporal integration at the core of SCZ constituting a “common currency” of neuronal, psychological, and phenomenological levels.     

Electrophysiologic evaluation of sinus node dysfunction in postoperative children and young adults utilizing combined autonomic blockade

Sinus node dysfunction is a recognized problem following surgery for congenital heart disease. Seven postoperative patients with sinus node dysfunction (5 Mustard, 1 tetralogy of Fallot, 1 Fontan) underwent electrophysiology study of sinus node function during combined autonomic blockade (CAB) utilizing propranolol 0.2 mg/kg i.v. and atropine 0.04 mg/kg i.v. to evaluate intrinsic sinus node function isolated from autonomic control. During CAB, intrinsic heart rate, intrinsic corrected sinus node recovery time, and intrinsic sinoatrial recovery time were measured. These results were compared with age-matched normal intrinsic data from our lab [normal (n = 7, mean age 9 years) IHR 128 +/- 24, intrinsic corrected sinus node recovery time 135 +/- 40 ms, intrinsic sinoatrial conduction time 86 +/- 19 ms]. Among postoperative Mustard patients (n = 5, mean age 13 years, mean years postoperative 11) 2 of 5 had clearly abnormal intrinsic sinus node function with nonsinus rhythm during CAB; 3 of 5 had sinus rhythm during CAB with normal or mildly abnormal intrinsic sinus node function. The postoperative case of tetralogy of Fallot (age 20 years, postoperative 14 years) had mildly abnormal intrinsic sinus node electrophysiology study. The postoperative case of Fontan (age 16 years, postoperative 1.5 years) had sinus rhythm at rest but left atrial rhythm during CAB. Different aspects of sinus node dysfunction may be expressed during resting electrophysiology study vs. electrophysiology study utilizing CAB. The pathophysiology of sinus node dysfunction among postoperative pediatric patients is not homogeneous with regard to the contribution of intrinsic sinus node dysfunction. In those patients with normal or mildly abnormal intrinsic sinus node function, an important pathophysiologic influence of the autonomic nervous system is implicated.     

Morphological pattern of intrinsic nerve plexus distributed on the rabbit heart and interatrial septum

Although the rabbit is routinely used as the animal model of choice to investigate cardiac electrophysiology, the neuroanatomy of the rabbit heart is not well documented. The aim of this study was to examine the topography of the intrinsic nerve plexus located on the rabbit heart surface and interatrial septum stained histochemically for acetylcholinesterase using pressure‐distended whole hearts and whole‐mount preparations from 33 Californian rabbits. Mediastinal cardiac nerves entered the venous part of the heart along the root of the right cranial vein (superior caval vein) and at the bifurcation of the pulmonary trunk. The accessing nerves of the venous part of the heart passed into the nerve plexus of heart hilum at the heart base. Nerves approaching the heart extended epicardially and innervated the atria, interatrial septum and ventricles by five nerve subplexuses, i.e. left and middle dorsal, dorsal right atrial, ventral right and left atrial subplexuses. Numerous nerves accessed the arterial part of the arterial part of the heart hilum between the aorta and pulmonary trunk, and distributed onto ventricles by the left and right coronary subplexuses. Clusters of intrinsic cardiac neurons were concentrated at the heart base at the roots of pulmonary veins with some positioned on the infundibulum. The mean number of intrinsic neurons in the rabbit heart is not significantly affected by aging: 2200 ± 262 (range 1517–2788; aged) vs. 2118 ± 108 (range 1513–2822; juvenile). In conclusion, despite anatomic differences in the distribution of intrinsic cardiac neurons and the presence of well‐developed nerve plexus within the heart hilum, the topography of all seven subplexuses of the intrinsic nerve plexus in rabbit heart corresponds rather well to other mammalian species, including humans.